In Vivo and in Vitro Blood–Brain Barrier Transport of 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitors

Akira Saheki, Tetsuya Terasaki, Ikumi Tamai, Akira Tsuji

Research output: Contribution to journalArticlepeer-review

177 Citations (Scopus)


Among the HMG-CoA reductase inhibitors, lovastatin and simvastatin have central nervous system (CNS) side effects, such as sleep disturbance, whereas pravastatin does not. This difference in CNS side effects may be due to a difference in blood–brain barrier (BBB) permeability among these inhibitors. To test this hypothesis, we compared the BBB transport ability of HMG-CoA reductase inhibitors by using an in vivo brain perfusion technique in rats and an in vitro culture system of bovine brain capillary endothelial cells. The in vivo BBB permeability coefficients of the lipophilic inhibitors, [14C]lovastatin and [14C]simvastatin, were high. In contrast, that of the hydrophilic inhibitor, [14C]pravastatin, was low and not significantly different from that of [14C]sucrose, an extracellular space marker. Similarly, the in vitro BBB permeability coefficients of [14C]lovastatin and [1C]simvastatin were high, while that of [14C]-pravastatin was low. The in vivo and in vitro transcellular permeabilities obtained for HMG-CoA reductase inhibitors were comparable. This study shows that the BBB permeability correlates with the CNS side effects of the HMG-CoA reductase inhibitors.

Original languageEnglish
Pages (from-to)305-311
Number of pages7
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Issue number2
Publication statusPublished - 1994 Feb
Externally publishedYes


  • 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor
  • blood–brain barrier (BBB) transport
  • brain perfusion
  • central nervous system (CNS) side effect
  • cultured brain capillary endothelial cell
  • lipophilicity
  • lovastatin
  • pravastatin
  • simvastatin

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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